Decreased prostatic arachidonic acid in human prostatic carcinoma.

OBJECTIVE: To measure prostatic and blood fatty acid composition in a large group of patients undergoing prostatectomy for benign or malignant prostate disease, as there is evidence linking arachidonic acid metabolism and prostate cancer through its role as an eicosanoid precursor, and earlier studies showed lower prostatic arachidonic acid content in a few patients. PATIENTS AND METHODS: Prostatic phospholipid fatty acid composition was determined in prostate tissue from 173 patients undergoing prostate surgery, i.e. radical prostatectomy, cystoprostatectomy or transurethral resection (TURP). Blood fatty acid composition was determined in 99 of these patients and in 85 undergoing prostatic needle biopsy. RESULTS: There was a significantly lower percentage of arachidonic acid in malignant than in benign portions of the prostate (15.2% vs 17%) in all patients assessed. The changes were greatest in those undergoing TURP for known prostate cancer (13.4% vs 17.2%), these patients having the greatest proportion of malignancy in the specimens. There were no consistent changes in blood fatty acid composition. CONCLUSION: This is the first prospective study of arachidonic acids levels involving many consecutive patients undergoing prostate surgery for either benign or malignant disease. The lower prostatic arachidonic acid level is probably a result of the increased use of arachidonic acid for producing prostaglandins and/or leukotrienes. Further understanding of the cause and/or consequence of this finding might lead to a better understanding of prostate cancer.

Primary pulmonary plasmacytoma: a case report.

Most extramedullary plasmacytomas are associated with the upper respiratory tract. Primary pulmonary plasmacytomas are rare, and the treatment is surgical excision. This malignancy advances to multiple myeloma in a minority of patients. The patient in our case report is the first to experience renal failure due to hematologic monoclonal gammopathy. Postoperatively, serum protein electrophoresis reverted to normal.

Utility of Wang needle aspiration in the diagnosis of actinomycosis.

An 85-year-old man had a 4-year history of recurrent pneumonia with a persistent pleural effusion. He underwent repeated bronchoscopy that revealed a right bronchus intermedius mass, but bronchial washes and biopsies remained nondiagnostic. A repeat bronchoscopy was performed, and a Wang needle aspiration of the mass was obtained that showed sulfur granules, diagnosing actinomycosis. The patient was started on appropriate antibiotic therapy. Actinomycosis must be considered in a patient with recurrent pneumonia and an endobronchial mass. Wang needle aspiration via bronchoscopy may be an important diagnostic tool.

Diagnostic value of brush cytology in the diagnosis of duodenal, biliary, and ampullary neoplasms.

Endoscopy is a valuable tool in the diagnosis and management of duodenal lesions and biliary strictures. We assessed the value of cytology in the evaluation of these lesions and analyzed the causes of discrepancy among clinical, histologic, and cytologic parameters. The study included 118 patients with duodenal ulcers, ampullary neoplasms, or biliary strictures who were examined between 1975 and 1995; 120 cytologic examinations were performed. The specimens included brushings of the duodenum (DB, n = 50), ampulla (AB, n = 32), and biliary ducts (BB, n = 38). Endoscopic biopsies performed concurrently included the duodenum (n = 37), the ampulla (n = 22), and the biliary ducts (n = 23). Comparison of cytologic and histologic results showed the following sensitivity and specificity: DB, 40% and 97%, respectively; AB, 100% each; BB, 75% and 93%, respectively. The DB, AB, and BB revealed malignant neoplasms in 2 of 5, 7 of 7, and 6 of 8 cases, respectively. Twenty-three duodenal neoplasms were diagnosed by either modality and included 11 adenocarcinomas, 9 villous tumors, 2 metastatic renal cell carcinomas, and 1 large cell non-Hodgkin's lymphoma. Endoscopic brush cytology is an effective means of diagnosing ampullary neoplasms, and it complements tissue biopsy in cases of bile duct stricture. Location, predominance of tumor-induced stroma, an extramucosal growth pattern, sampling error, and interpretative experience influence the diagnostic evaluation. Cytologic diagnosis of an adenoma does not exclude an underlying malignant neoplasm in ampullary tumors. In some instances, it may be difficult to distinguish between villous tumors with severe dysplasia and adenocarcinomas by cytology alone.

Neurotic effects of doxycycline sclerotherapy.

A patient experienced phrenic nerve paralysis after doxycycline sclerotherapy for treatment of chylous fistula at our institution. The purpose of this study is to use physiologic testing to determine whether doxycycline is capable of inducing defects in neural function. A nonrandomized, controlled trial was performed with nerve-conduction studies to determine possible deleterious effects of doxycycline sclerotherapy. Thirty-eight CD rats were used and separated into four groups. Doxycycline was applied to the sciatic nerves of rats by either topical application directly on the nerve or by intraneural injection. Nerve-conduction studies were done before surgery and at 1,7, and 21 days after surgery. The results showed a statistically significant decrement in nerve-conduction velocity and strength of transmitted impulse in those nerves injected with doxycycline solution. Complete nerve block was seen frequently. This effect was not seen with topical application of doxycycline or normal saline solution or with intraneural injection of normal saline solution. This study demonstrates that doxycycline can induce a marked decrement in neural function when applied to the subepineural layers of the sciatic nerve in the rat. Therefore doxycycline sclerotherapy should be used with great caution in situations in which it could become exposed to nerves that have sustained surgical trauma.

Postsegmentectomy pseudotumor of the lung.

After an apicoposterior staple segmental resection for squamous cell carcinoma of the left upper lobe, a "new" mass developed in the remaining upper lobe, 8 months postoperatively. Upon removal, this proved to be an ischemic infarction in the anterior segment. Residual lung rotation may have compounded local lung ischemia secondary to the staple technique of resection. One clue to this pseudotumor development appears to be prolonged postoperative "haziness" on chest roentgenograms.

Cytologic findings in thyroglossal duct carcinoma.

Approximately 150 cases of thyroglossal duct carcinoma, predominantly of the papillary type, have been reported, but the preoperative fine-needle aspiration (FNA) diagnosis of such neoplasms has rarely been cited. The authors describe FNA findings in four samples obtained from three patients who were 29, 50, and 83 years of age, histologically diagnosed as papillary (n = 2) and squamous (n = 1) thyroglossal duct carcinomas. Atypia and squamous cell carcinoma were the FNA diagnoses in the patients with papillary carcinomas. The remaining case was correctly diagnosed as keratinizing squamous cell carcinoma. Cellularity was scant in two cases and moderate in one, and all displayed a cystic background. The authors also reviewed FNA features in 11 papillary and 2 Hurthle cell carcinomas from the English language literature; diagnostic findings were present in less than one third of the cases. In conclusion, familiarity with the FNA findings of thyroglossal duct carcinoma is limited by its rarity. The presence of large, atypical squamous cells, or psammoma bodies, in the FNA material of a midline anterior cystic neck mass should suggest papillary thyroglossal duct carcinoma.

Histologic effect of doxycycline sclerotherapy on rat femoral nerve.

BACKGROUND: This study stems from an encounter with a phrenic nerve paralysis in a patient following doxycycline sclerotherapy for treatment of chylous fistula. The purpose of this study is to identify possible histologic evidence of doxycycline-induced nerve injury. METHODS: The femoral nerves of CD rats were used as the in vivo animal model. The nerves were exposed to varying concentrations doxycycline and normal saline was the control. The nerves were studied at several time intervals using two different staining techniques. RESULTS: The results suggest that topical doxycycline induces tissue reactions which are different from normal saline. These reactions include stimulation of a local giant cell inflammatory reaction and disruption of the myelin sheath. CONCLUSIONS: Despite the fact that this study does not give physiologic evidence of neurotoxicity, the histologic results suggest that topical doxycycline may cause nerve damage directly or indirectly. We conclude that doxycycline should not be used for sclerotherapy where unprotected nerves are exposed to the agent until further physiologic tests are performed to prove its safety.

In situ apoptosis assay for the detection of early acute myocardial infarction.

Detection and age determination of myocardial infarction (MI) is often necessary in both clinical and pathological settings. Conventional histopathological techniques are of limited utility in the demonstration of myocardial ischemic cell death (MICD) within the first 6 hours of MI. In this study, an in situ apoptosis assay was evaluated for the determination of early MICD or early MI. Sections of formalin-fixed, paraffin-embedded archival tissue blocks from 80 hearts were stained for the presence of apoptotic cells by specific labeling of nuclear DNA fragmentation. Conventional hematoxylin and eosin stain showed acute MI (group A, n = 32), equivocal evidence for MICD or early infarction (group B, n = 35), or no abnormal findings (group C, n = 13). The sensitivity and specificity of the in situ apoptosis assay for MICD were confirmed in groups A and C patients. We showed that apoptosis of myocardial cells can occur after ischemic myocardial cell injury. Virtually all documented cases of acute MI (group A) revealed a sizeable distribution of apoptotic cells visible on gross examination of glass slides. Special attention was given to patients in group B, who were at high risk for MI and for suspected but not proved cardiac death. In this group, 34/35 cases (97%) showed focal or diffuse nuclear positivity of varying degrees for apoptosis, confirming the presence of MICD. A sizeable distribution of apoptotic cells, similar to that observed in group A, was noted in 13/35 cases (37%) of group B, suggesting acute MI in these cases. The in situ assay of DNA fragmentation can detect MICD while the histological diagnosis is still inconclusive. It is estimated that with this assay one can detect MICD as early as 2 to 4 hours.

Apoptosis is a major pathway responsible for the resolution of type II pneumocytes in acute lung injury.

Proliferation of type II pneumocytes has been linked to a repair process during the early phase of acute lung injury, and it persists for a variable period. The mechanisms responsible for their dissolution and/or disappearance are not known, but we speculate that it may be partly due to apoptosis. Sections of lung tissue from patients with acute lung injury (n = 7) and chronic interstitial pneumonia (n = 14) were stained for detection of apoptotic cells via specific labeling of nuclear DNA fragmentation. Results were correlated with those of proliferating cell nuclear antigen (PCNA) staining for cell proliferation. Marked apoptosis of CD68-negative type II pneumocytes (30 to 80%) was detected in four of the seven (57%) cases of acute lung injury. In these cases, representing the resolution phase of acute lung injury, PCNA positivity in pneumocytes was extremely rare. In the 3 other cases in the acute/proliferative phase, apoptotic type II pneumocytes were rare whereas PCNA expression was quite evident in these cells. In chronic interstitial pneumonia, only rare type II pneumocytes (< 5%) exhibited apoptosis, and they showed variable staining for PCNA (up to 70%). We conclude that proliferation of type II pneumocytes occurs during the early phase of acute lung injury and is of variable extent and duration. In the resolution phase of acute lung injury, extensive apoptosis of type II pneumocytes is largely responsible for the disappearance of these cells. The time frame within which the apoptotic response occurs is variable and is likely to be dependent upon the specific etiology and extent of the injury. In chronic interstitial pneumonia, type II pneumocytes proliferate continuously, although to a much lesser degree than in the early phase of acute lung injury, and are minimally apoptotic.

Secondary pericardial malignancies: a critical appraisal of the role of cytology, pericardial biopsy, and DNA ploidy analysis.

The authors studied 112 pericardial fluids (45 malignant, and 67 benign) from 63 men and 33 women. All cytologic (n = 112) and histologic (n = 61) specimens were reviewed. Statistical analysis was conducted in 61 paired cytology and histology specimens (45 malignant and 16 benign) and correlated with available ploidy analysis of fluid specimens (n = 34). In cases of malignancy (41 patients), the primary site was known in 34 patients, whereas no origin for metastatic disease was apparent in 3 patients. Pericardial cytology yielded the initial diagnosis in four patients. After careful review of all cytology and histology specimens, seven truly discrepant cases were noted, six of which had positive cytology. Tissue biopsy sampling error was the cause for such discrepancies. DNA diploidy obtained by flow cytometry correlated with benign cytology, whereas aneuploidy was associated with malignant cytology in a total of 32 of 34 cases (94%). Cytologically malignant effusions rendered diploid DNA in 2 of 10 cases (20%). In conclusion, cytology is the single most important parameter in the evaluation of secondary pericardial malignancy and should be considered the gold standard. Causes for false-negative cytologic diagnoses include scant cellularity and obscuring blood. Hence, careful screening is recommended. The low sensitivity of flow cytometric DNA analysis does not favor its routine use.

Second primary lung cancer.

We reviewed our experience with second primary lung cancer (SPLC) at the Little Rock Veterans Affairs Medical Center from 1966 to 1993. Fifty-four patients were found to have 65 such lesions after 1,572 "curative" resections for lung cancer (4.1%). Eleven patients had at least a third primary tumor (3 having more). Metachronous SPLCs comprised 60% (39/65) and synchronous 40% (26/65). The mean interval between first and second tumors was 54.63 +/- 8 (standard error) months (range, 5 to 218 months), and that between second and third was 26.1 +/- 7.4 (standard error) (range, 5.5 to 51 months). Squamous cell carcinoma comprised 58.4% (38/65), adenocarcinoma 30.8% (20/65), and small cell carcinoma 10.8% (7/65). Histology of the SPLC was the same as that of the first tumor in 50.7% (33/65). Stage I primary tumors comprised 76% (41/54) of index tumors, 61.1% (33/54) of SPLCs, and 72.2% (8/11) of third primary tumors. Second primary lung cancer followed minimal resection in 44% (24/54), lobectomy in 37% (20/54), and pneumonectomy in 13% (7/54) of cases. There was no evidence that minimal resection for the first primary tumor predisposed to SPLC. After 1983 the majority of SPLCs were diagnosed with computed tomographic scanning. After resection of SPLCs, survival rates at 3 and 5 years were 26% and 18%, metachronous 39% and 23.4%, and synchronous 12.25% and 12.25%.

Bilateral endobronchial non-Hodgkin's lymphoma.

Pulmonary involvement with non-Hodgkin's lymphoma, while well recognized, is less common than with Hodgkin's lymphoma. Endobronchial non-Hodgkin's lymphoma is even rarer and usually occurs in the presence of disseminated disease. We present a case of bilateral endobronchial non-Hodgkin's lymphoma.

Isolated symptomatic midcervical stenosis of the internal carotid artery.

All carotid arteriograms performed between January 1, 1986 and December 31, 1991 were reviewed for instances of midcervical carotid stenosis. Sixteen cases were identified. A stenosis related to the hypoglossal nerve was specifically identified in three operative reports in the retrospective review. Pathologic examinations of the specimens confirmed the presence of atherosclerotic plaque or fibrous dysplasia. In another case, relief of intermittent neurologic symptoms (TIAs) was obtained by division of the stylohyoid ligament. Prospective observation of five cases confirmed a stenosis immediately distal to a transverse neurofascial band formed by the hypoglossal nerve, which arose with the vagus nerve in three patients, and a large cervical contribution to the ansa hypoglossi in two. Presumably the lesion was caused by the turbulent flow in the internal carotid artery distal to the band. Isolated stenosis of the midcervical internal carotid artery unrelated to bifurcation disease may be the result of turbulence induced by tethering neural or myofascial bands.

Pulmonary artery sleeve resection for abutting left upper lobe lesions.

Because the left upper lobe bronchus overlies the left pulmonary artery (PA), T2-3 lesions, N0-1 disease, or rarely inflammation may involve this vessel, necessitating lobectomy with partial PA resection or pneumonectomy with sacrifice of the lower lobe. In 486 operations performed for left upper lobe lesions between 1966 and 1992 (wedge, 111; segmentectomy, 131; lobectomy, 155; pneumonectomy, 89), isolated PA encroachment was caused by bronchogenic carcinoma (32), invasive aspergillosis (2), or organized pneumonitis (1) and occurred in 9% (32/360) of malignant left upper lobe tumors and 2% (3/126) of benign lesions. Initially (1966 through 1979), PA involvement was the indication for 30% (18/60) of left pneumonectomies. Later (1980 through 1990), tangential resection of the PA was attempted in 11, 5 ending up with pneumonectomy. Overall, 35 of 244 patients undergoing major left upper lobe resection (lobectomy or pneumonectomy) had PA encroachment. Recently, we have performed, selectively in patients with restricted lung function, six left upper lobectomies with sleeve resection of the PA. Paneled saphenous vein interposition was used (3) or 18-mm polytetrafluorethylene tube prostheses (3). All patients survived, 1 later requiring completion pneumonectomy for bronchostenosis after wedge bronchoplasty. Two have since died of metastases or pulmonary insufficiency; the remainder (average follow-up, 17 months) are asymptomatic with lower lobe function in 3 confirmed by differential ventilation-perfusion scans and pulmonary angiography.

Gallbladder and gastric argyrophil carcinoid associated with a case of Zollinger-Ellison syndrome.

Gastric carcinoids are uncommon tumors, reportedly associated with pathological hypergastrinemic states such as Zollinger-Ellison syndrome (ZES). Gallbladder carcinoids are also very rare, but have not previously been reported in association with ZES. In this report we discuss a patient with ZES in whom both gastric and gallbladder carcinoid tumors were found.

When is polypectomy sufficient treatment for colorectal cancer in a polyp?

Eighty-seven patients with a carcinoma in a polyp were reviewed over a 12-year period. Ten histologic criteria were analyzed for an association with the presence of residual carcinoma. Four factors were identified as having prognostic value: size greater than 1.5 cm, sessility, cancer of at least 50% of the adenoma volume, and invasive carcinoma. Polypectomy alone is adequate treatment unless the carcinoma invades deeper to the muscularis mucosa and is associated with one or more of these characteristics.

Ultrastructure of metastatic rete testis adenocarcinoma.

Adenocarcinoma of the rete testis is a rare tumor. We describe the ultrastructural appearance of a retroperitoneal adenocarcinoma metastatic from the rete testis, and compare this appearance with that of normal human rete testis. Both normal rete epithelium and the tumor showed deep, narrow nuclear invaginations with apparent nuclear lobulation; small, pleomorphic, electron-dense, membrane-bound granules in the basal cytoplasm; lipid droplets in the apical cytoplasm; and distinctive bulbous cytoplasmic projections along the apical surfaces of the cells. In addition, more general features of glandular tissue were seen. Features notable for their absence were mucin granules, microvilli containing filamentous cores, glycocalyx, and glycocalyceal bodies. The ultrastructural appearance was sufficiently distinctive to suggest that, in the proper clinical context, electron microscopy may serve to support a diagnosis of adenocarcinoma of the rete testis.

Combination and individual antitumor effects of hyperthermia, cisplatin, and selected dithiocarbamates.

The antitumor effects produced by combinations of cisplatin (Pt), substituted dithiocarbamates (dimethyldithiocarbamate [DmDTC] and sodium N-methyl-D-glucamine dithiocarbamate [NMGDTC]) and hyperthermia (H) were measured and compared to those produced by single agents alone in C3H/HeN mice bearing the transplantable radiation-induced fibrosarcoma, RIF-1, in one or both hind feet. The average tumor volumes of control and treatment groups were compared periodically after treatment with H. Combinations of H and Pt completely resolved established foot tumors in 10/13 mice. However, evidence of long-term nephrotoxicity and gastrointestinal (GI) toxicity became evident causing death of these mice within 120 to 122 days after tumor inoculation. Hyperthermia plus DmDTC resolved tumors in heated and non-heated feet in 3/8 mice, thus demonstrating both ipsilateral and contralateral anti-tumor activity. Furthermore, H-Pt-NMGDTC produced complete tumor resolution in 7/13 mice; these mice survived and were tumor-free 180 days post inoculation and autopsies revealed no appreciable nephro- or GI toxicity. In addition, 4/8 mice underwent complete tumor resolution in heated left feet plus dramatic retarding of tumor growth in unheated right feet (ipsilateral and contralateral anti-tumor effects). Five heat-treated left foot tumors resolved in the H-Pt-DmDTC group with one mouse demonstrating resolution of tumor in both feet. Advanced foot tumors were treated with H-DmDTC and H-Pt-DmDTC. Hyperthermia and Pt were administered on day 0 of the experiment and DmDTC on days 0 through 3; dramatic tumor shrinkage continued through day 6 for a total of 75 to 80 percent reduction of tumor volume in both groups. The concurrent administration of DmDTC or NMGDTC with H and Pt prevented or greatly reduced nephrotoxicity and GI toxicity in all experiments without retarding anti-tumor efficacy.